Subacute oral toxicity study of benzyl isothiocyanate in rats

Lewerenz, H. J.; Bleyl, D. W. R.; Plass, R.

doi:10.1002/food.19920360213

Cited by 24 publications

(13 citation statements)

References 15 publications

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“…On the other hand, AITC was previously reported to induce renal microscopic changes such as dilatation of distal tubules and increased desquamation in rats given a dose of 20 mg/kg body weight/day by gavage for 6 weeks (Lewerenz et al, 1988). T-Cho was also found to be decreased with a dose-dependence in females given HRE, whereas among ITCs, BITC was reported to increase serum cholesterol levels (Lewerenz et al, 1992). Although the composition of the test substance and the procedure for administration were different, the cause of these discrepancies may be due to some other factors.…”

Section: Discussionmentioning

confidence: 90%

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats

et al. 2011

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-Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

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Section: Discussionmentioning

confidence: 90%

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats

et al. 2011

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“…Warin et al [20] reported previously that the administration of BITC at 1 and 3 mmol/kg for 25 weeks did not induce weight loss or any other adverse effect in the MMTV-neu mice. However, several studies reported that various ITCs cause toxicity in the kidney and liver when administered at relatively high doses (20-200 mg/kg body weight/day) [33][34][35][36][37]. In order to determine whether BITC causes toxicity in the kidney at the doses used in this study, we measured the serum levels of creatinine, an indicator of renal function.…”

Section: Discussionmentioning

confidence: 99%

Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice

Kim

Hong

Eom

et al. 2010

Breast Cancer Res Treat

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Benzyl-isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has also been shown to have anti-tumor properties. To evaluate the effects of BITC administration on the tumor growth and metastasis of breast cancer, 4T1 murine mammary carcinoma cells were injected into the inguinal mammary fat pads of syngeneic female BALB/c mice. One day later, the mice were subjected to gavage for 4 weeks with BITC (0, 5, or 10 mg/kg body weight/day). Oral BITC treatment induced a significant reduction in the growth of solid tumors. BITC reduced hemoglobin contents and CD31 and vascular endothelial growth factor (VEGF) expression in the tumors, as well as circulating levels of VEGF. Reduced expressions of proliferating cell nuclear antigen and cyclin-dependent kinase 4 were noted in the tumors of BITC-treated mice. BITC markedly increased the numbers of apoptotic cells with increased Bax expression, cleaved caspase-3, and PARP levels, but reduced Bcl-2 expression in tumor tissues. In addition, BITC was shown to reduce the numbers of pulmonary tumor nodules and the total pulmonary metastatic volume. BITC induced a significant reduction in the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and urokinase-type plasminogen activator in the sera and lungs of 4T1 cell-injected mice. However, the concentrations of TIMP-2 and plasminogen activator inhibitor-1 were increased in the sera and lungs of BITC-treated mice. The results of this study indicate that BITC has potential as a preventive agent for metastatic breast cancer.

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“…BITC, a potential chemopreventive agent (Wattenberg, 1983) has been shown to be toxic to some cells/tissues in vitro and in vivo. Male rats exposed to BITC (orally) showed significant histological changes in some organs and tissues (Lewerenz, 1992). Rats exposed to BITC (0.1% in the diet) were also reported to show prominent characteristics of toxicity like single cell necrosis, cytoplasmic vacuolation, erosion and haemorrhage of the urinary bladder (Akagi et al, 2003).…”

Section: Discussionmentioning

confidence: 97%

“…Lewerenz et al (1992) reported that oral exposure of male rats to high concentrations of BITC caused peritonitis, adhesions between the diaphragm, stomach, spleen, pancreas and liver. It is thus envisaged that at the toxic level that will be needed to kill and expel intestinal worms in vivo, BITC may also cause impairment of intestinal motility and functions.…”

Section: Discussionmentioning

confidence: 98%

Modulation of Jejunal Contractions by Extract of Carica papaya L. Seeds

Adebiyi

Adaikan

2005

Phytotherapy Research

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Carica papaya L. (papaya) seed preparations are used in traditional medicine to expel intestinal worms in human and ruminants. In the present study, an ethanol extract of papaya seeds (EEPS; 0.1-6.4 mg/mL) caused concentration-dependent inhibition of jejunal contractions in contrast to corresponding concentrations of DMSO (solvent control). The inhibitory effect of EEPS on jejunal contractions was significantly irreversible. Previous studies have indicated that benzyl isothiocyanate (BITC) is the main bioactive compound responsible for the anthelmintic activity of papaya seeds. In the present study, standard BITC (0.01-0.64 mmol/L) also caused significant irreversible inhibition of jejunal contractions. Recovery of jejunal contractions after BITC-induced inhibition was weaker than recovery after EEPS-induced inhibition (BITC versus EEPS: 19 +/- 7% vs 38 +/- 13%). Cryosections of the jejunum showed marked morphological damage of the segments treated with BITC in contrast to DMSO-treated segments. EEPS-induced jejunal damage was, however, less marked. These results indicate that papaya seed extract and BITC, its principal bioactive constituent are capable of weakening the contractile capability of rabbit isolated jejunum. It is thus envisaged that at the toxic level that will be needed to kill and expel intestinal worms in vivo, BITC may also cause impairment of intestinal functions.

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Subacute oral toxicity study of benzyl isothiocyanate in rats

Cited by 24 publications

References 15 publications

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats

Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice

Modulation of Jejunal Contractions by Extract of Carica papaya L. Seeds

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